(September 5th, 2017) Just a few nanogram per kg body weight can kill a human. Recently, scientists in Sweden and the US discovered a new form of botulinum toxin.
Botulinum neurotoxins, commonly known as ‘botox’, have wide-ranging uses in medicine and the cosmetic business. These neurotoxins are some of the most potent known to man and are produced by the bacterium, Clostridium botulinum. In tiny doses, botulinum neurotoxins can be effective in reducing wrinkles, sweaty palms, twitching eyes, overactive bladders, as well as many other neuromuscular conditions. They do so by preventing neurotransmitter release, blocking signals between nerves and muscles, causing the muscles to relax. Recent evidence also suggests the toxin may be effective in treating migraines and depression, although how it works for these conditions, is not yet entirely clear.
The first botulinum neurotoxin was discovered in 1919 and, until recently, it was known that there were seven types of botulinum toxin, named type A–G Botulinum Neurotoxin (BoNT/A-G). In the last 40 years, no new versions of the neurotoxin were discovered, until surprisingly, scientists recently revealed an 8th version - through published genomic sequence searches - and named it type X (BoNT/X).
This work resulted from research led by Pål Stenmark of Stockholm University’s Department of Biochemistry and Biophysics, in collaboration with Min Dong at Harvard Medical School. Stenmark says he became interested in this research area as he was “fascinated by the complexity of these toxins and the possibility to contribute to the development of new therapeutics”. Indeed, as he describes, the discovery of this new version of the toxin “presents a new, potential therapeutic toxin for modulating secretions in [nerve] cells”. This is important, since repeated treatment with the same botulinum toxin can lead to early development of antibodies, making the injections ineffective.
Despite the therapeutic potential of the botulinum neurotoxins, they can also cause the often fatal condition, botulism. When ingested in large doses this leads to the paralysis of key muscles, also those necessary for breathing. One of the most common causes of food-borne botulism is improperly home-canned food, especially low-acid foods, such as vegetables and meats, when a temperature of 115°C, suitable to destroy the spores, is not reached.
Due to the lethality of botulinum toxins, as stated in the paper, they are “classified as one of the six most dangerous potential bioterrorism agents”. Therefore, according to Stenmark, the discovery of this new version of the toxin was also significant because “it is important to identify and characterise all of the clostridial toxins. Only then can we develop detection methods and antidotes against them”. Perhaps, a little alarmingly, the paper states that at the moment “no antisera against BoNT/X are available”. Stenmark remarked that working with the toxin, like all other botulinum toxins was problematic, since “these toxins are very dangerous. We only work with inactivated toxin or very small amounts of active toxin”.
Altogether, according to Stenmark, “the work took approximately 1.5 years” and “the key finding was the identification of the toxin itself, proving that it is active and the finding that it cleaves new additional targets in our cells”. However, it appears this paper is only the beginning of the story. Stenmark says that following on from this work, his group “plans to determine the structure of the toxin and investigate how it binds to the nerve cell. They will also investigate how the unique properties of BoNT/X can be best used to develop new therapeutics”.
So, let’s hope an antidote to this new neurotoxin is developed quickly and that this potential bio-weapon is only used for therapeutic purposes.